Imaging-based diagnosis of sarcopenia for transplant-free survival in primary sclerosing cholangitis.

BACKGROUND: Imaging-based assessment of sarcopenia is a well-validated prognostic tool for patients with chronic liver disease. However, little is known about its value in patients with primary sclerosing cholangitis (PSC). This cross-sectional study aimed to investigate the predictive value of the cross-sectional imaging-based skeletal muscle index (SMI) for transplant-free survival (TFS) in patients with PSC. METHODS: A total of 95 patients with PSC who underwent abdominal cross-sectional imaging between 2008 and 2022 were included in this retrospective study. SMI was measured at the third lumbar vertebra level (L3-SMI). The cut-off values to define sarcopenia were < 50 cm²/m² in male patients and < 39 cm²/m² in female patients. The primary outcome of this study was TFS, which was defined as survival without liver transplantation or death from any cause. RESULTS: Our study indicates that L3-SMI sarcopenia impairs TFS in patients with PSC (5-year TFS: 33.9% vs. 83.3%, p = 0.001, log-rank test). L3-SMI sarcopenia was independently associated with reduced TFS via multivariate Cox regression analysis (HR = 2.749; p = 0.028). Body mass index reduction > 10% at 12 months, which is used as MELD standard exception (SE) criterion in Eurotransplant (in Germany only until September 2023), was not significantly associated with TFS in the multivariate Cox regression analysis (HR = 1.417; p = 0.330). Substitution of BMI reduction with L3-SMI in the German SE criteria improved the predictive accuracy of TFS compared to the established SE criteria (multivariable Cox regression analysis: HR = 4.007, p < 0.001 vs. HR = 1.691, p = 0.141). CONCLUSION: Imaging-based diagnosis of sarcopenia via L3-SMI is associated with a low TFS in patients with PSC and may provide additional benefits as a prognostic factor in patient selection for liver transplantation.

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. METHODS: A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n = 290). Medical data and overall survival (OS) were assessed. A Cox regression model was used to create an alternative prediction model, which includes significant prognostic factors. RESULTS: Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced median survival of 5.0 (3.1-6.9) months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9-5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh, MELD, MELD-Na score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation. CONCLUSIONS: The FIPS score is superior to established scoring systems for the identification of high-risk patients with a worse prognosis following elective TIPS implantation. LAY SUMMARY: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.

Bile Acids in Control of the Gut-Liver-Axis.

The liver and gut share an intimate relationship whose communication relies heavily on metabolites, among which bile acids play a major role. Beyond their function as emulsifiers, bile acids have been recognized for their influence on metabolism of glucose and lipids as well as for their impact on immune responses. Therefore, changes to the composition of the bile acid pool can be consequential to liver and to gut physiology. By metabolizing primary bile acids to secondary bile acids, the bacterial gut microbiome modifies how bile acids exert influence. An altered ratio of secondary to primary bile acids is found to be substantial in many studies. Thus, disease pathogenesis and progression could be changed by gut microbiome modification which influences the bile acid pool.

Evaluation of impact of elective invasive examinations in patients with transjugular intrahepatic portosystemic shunt in the long-term follow up.

INTRODUCTION: In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce. AIM: The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS: Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed. RESULTS: No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure. CONCLUSION: The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction.

Digital single-operator cholangioscopy: a useful tool for selective guidewire placements across complex biliary strictures.

BACKGROUND: Treatment of biliary strictures is challenging. Digital single-operator cholangioscopes (SOCs) equipped with an improved imaging quality, were recently introduced and may be useful for selective guidewire placement in difficult biliary strictures. METHODS: A total of 167 digital SOC procedures performed between 2015 and 2018 were retrospectively analyzed for successful guidewire placements across biliary strictures. Only cases with previous failed conventional guidewire placement approaches were included. RESULTS: In total, 30 examinations with a digital SOC-assisted guidewire placement across biliary strictures, performed in 23 patients, were identified. In 52% of all patients, the stricture was benign with post-liver-transplant strictures (75%) as the most frequent finding; in 48% of all patients the stricture was malignant with cholangiocellular carcinoma as the most frequent type (64%). Guidewire placement was successful in 21 of 30 procedures (70%). According to a subgroup analysis, digital SOC-assisted guidewire placements were significantly more successful in patients with benign strictures than those in patients with malignant strictures (88.2% vs. 46.2%; p = 0.02). Furthermore, the technical success rate tended to be increased in cases of initial examinations (78.3%) than in patients with repeated examinations (42.9%; p = 0.15). Adverse events, such as post-interventional pancreatitis or cholangitis as well as severe bleeding occurred in 16.7% of all examinations. CONCLUSIONS: Digital SOC-assisted guidewire placements have high technical success rates, especially in benign biliary strictures. This technique can help to avoid more invasive procedures such as percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage.

Cost-Effectiveness of Access Expansion to Treatment of Hepatitis C Virus Infection Through Primary Care Providers.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is a major burden on individuals and health care systems. The Extension for Community Healthcare Outcomes (Project ECHO) enables primary care providers to deliver best-practice care for complex conditions to underserved populations. The US Congress passed the ECHO Act in late 2016, requiring the Department of Health and Human Services to investigate the model. We performed a cost-effectiveness analysis to assess diagnosis and treatment of HCV infection in a primary care patient panel with and without the implementation of Project ECHO. METHODS: We used Markov models to simulate disease progression, quality of life, and life expectancy among individuals with HCV infection and for the general population. Data from the University of New Mexico's ECHO operation for HCV show an increase in treatment rates. Corresponding increases in survival, quality-adjusted life years (QALYs), costs, and resulting budget impact between ECHO and non-ECHO patients with HCV were then compared. RESULTS: Project ECHO increased costs and QALYs. The incremental cost-effectiveness ratio of ECHO was $10,351 per QALY compared with the status quo; >99.9% of iterations fell below the willingness-to-pay threshold of $100,000 per QALY. We were unable to confirm whether the increase in rates of treatment associated with Project ECHO were due to increased or more targeted screening, higher adherence, or access to treatment. Our sensitivity analyses show that the results are largely independent of the cause. Budget impact analysis shows payers would have to invest an additional $339.54 million over a 5-year period to increase treatment by 4446 patients, per 1 million covered lives. CONCLUSION: Using a simulated primary care patient panel, we showed that Project ECHO is a cost-effective way to find and treat patients with HCV infection at scale using existing primary care providers. This approach could substantially reduce the burden of chronic HCV infection in the United States, but high budgetary costs suggest that incremental rollout of ECHO may be best.

Risk factors for allograft failure in liver transplant recipients.

BACKGROUND: With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. MATERIAL AND METHODS: A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. RESULTS: The mean age of recipients at the time of LT was 50.3 ±â€Š12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ±â€Š15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p < 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis in the initial protocol biopsy during follow-up (p = 0.001) to be recipient-related significant and independent risk factors for allograft failure following LT. CONCLUSION: Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine.

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.

Endocuff-assisted colonoscopy: a new accessory to improve adenoma detection rate? Technical aspects and first clinical experiences.

BACKGROUND AND STUDY AIMS: The Endocuff is a new colonoscopy accessory that has been designed to improve both the adenoma detection rate and endoscope tip control. PATIENTS AND METHODS: A total of 50 Endocuff-assisted colonoscopies were analyzed retrospectively with regard to safety, procedural success, and complications. RESULTS: The cecal intubation rate was 98 %, and the mean intubation time was 6.0 minutes (95 % confidence interval 5.3 - 6.6 minutes). The ileal intubation rate was 76 %. In 30 % of patients, the Endocuff caused small, superficial, "scratch-like" mucosal lesions. In all other patients, no Endocuff-associated complications were observed. A total of 36 adenomas were detected in 50 patients. The adenoma detection rate was 34 %. CONCLUSIONS: Endocuff-assisted colonoscopy showed good procedural success rates in terms of cecal intubation rate and time, and a promising adenoma detection rate. Endocuff seems to improve endoscope tip control, especially during polypectomy. Endocuff may be a useful device for colorectal adenoma screening, and should be investigated in larger trials.

Single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreaticography in patients with surgically altered anatomy: higher failure rate in malignant biliary obstruction - a prospective single center cohort analysis.

INTRODUCTION: The performance of endoscopic retrograde cholangiopancreaticography (ERCP) in patients with post-surgically altered anatomy is technically ambitious. Our study aimed at comparing a cohort of patients having successfully undergone single-balloon enteroscopy (SBE)-assisted ERCP to those in whom SBE-ERCP failed. METHODS: This trial is a prospective single center cohort study. Participants included 30 patients (median age 69.5 years, range 20-86 years) with previous pancreaticobiliary surgery. First, a conventional ERCP approach was attempted in all patients. Additionally, those patients in whom prior conventional ERCP had failed underwent SBE-ERCP (n = 26). Patients' baseline characteristics were retrieved and patient cohorts with and without successful SBE-ERCPs were compared and analyzed. Statistical analysis was applied. Univariate analysis was performed to detect possible risk factors of SBE-ERCP failure. RESULTS: The overall success rate of SBE-ERCP, including two patients with percutaneous transhepatic cholangiography- assisted rendezvous technique was 65.4% (17/26). Patients with malignant obstructive cholestasis had a significantly higher failure rate compared to those with benign strictures (84.2% vs. 14.2%, p < 0.001). DISCUSSION: SBE-ERCP is a promising tool for diagnostic and therapeutic procedures in the pancreaticobiliary system of selected, previously operated patients with failure of conventional ERCP. However, higher failure rates in malignant biliary obstruction should be taken into account.

Clearance of refractory bile duct stones with Extracorporeal Shockwave Lithotripsy: higher failure rate in obese patients.

OBJECTIVE: Bile duct stones that cannot be removed endoscopically are still a challenge in interventional gastroenterology. Extracorporeal shockwave lithotripsy (ESWL) with subsequent endoscopic extraction of residual fragments is an established treatment option if other endoscopic means are not successful. Our study aimed to investigate the efficacy and safety of ESWL for clearance of refractory bile duct stones. MATERIAL AND METHODS: A total of 73 consecutive patients treated for refractory choledocholithiasis with ESWL were retrospectively analyzed. Success and complication rates were calculated. RESULTS: Complete stone clearance was achieved in 66 cases (90%). Patients with complete clearance had a significantly lower body mass index or BMI (25.55 ± 5.01 kg/m² vs. 31.60 ± 6.26 kg/m², p = 0.035) and needed less ESWL treatments (3.61 ± 1.87 vs. 5.00 ± 1.63, p = 0.048). A relevant drop of hemoglobin occurred significantly more often in the group with partial clearance (43% vs. 6%, p = 0.005). CONCLUSIONS: ESWL proves to be an excellent clearing approach to refractory bile duct stones with high success rates. However, obesity is one risk factor for ESWL failure and higher procedural hazard.

Elevated Colon Cancer Rates Linked to Prior Appendicitis: A Retrospective Cohort Study Based on Data from German General Practices.

Background/Objective: The association between appendicitis and colon cancer is not yet fully understood. Previous studies have shown contradictory results. Currently, no population-based data from Germany are available with regard to the incidence of colon cancer following appendicitis. This study investigated the association between appendicitis and the incidence of colon cancer in Germany. Methods: In this retrospective cohort study, the incidence of colon cancer was compared for patients with appendicitis and patients without appendicitis, matched for age, sex, index year, average annual consultation frequency, and comorbidity. The aim of the study was to explore the relationship between appendicitis and the incidence of colon cancer. The evaluation was carried out using logistic regression analyses. Results: The study included 49,790 people with and without appendicitis, with a median age of 41 years. During a follow-up period of up to 15 years, 1.04% of cases with appendicitis and 0.60% of cases without appendicitis were newly diagnosed with colon cancer, with some 36.4% of colon cancer cases diagnosed within the first six months after appendicitis. Regression analyses revealed a significant association between appendicitis and colon cancer, particularly in men and in the age groups 41-50 (HR: 10.30; 95% CI: 1.03-43.82) and 18-30 years (HR: 8.17; 95% CI: 1.03-64.58). Conclusions: The present retrospective cohort study suggests an association between appendicitis and the incidence of colon cancer in Germany. Based on our results, we recommend offering a colonoscopy or at least a stool test within 12 months after appendicitis, especially for 18-50-year-olds and >60-year-olds in good general health.

Miniprobe endoscopic ultrasound accurately stages esophageal cancer and guides therapeutic decisions in the era of neoadjuvant therapy: results of a multicenter cohort analysis.

BACKGROUND: Despite recent advances in imaging techniques, adequate classification of esophageal lesions is still challenging. Accurate staging of tumors of the esophagus is a precondition for targeted therapy. In this retrospective, multicenter study, we report the role of high-frequency endoscopic ultrasound (EUS) catheter probes in pretherapeutic staging of esophageal neoplasms and thus guiding treatment decisions. METHODS: A total of 143 patients (mean age of 63.8 ± 10.7 years) with esophageal carcinoma were recruited from five German centers (Münster, Oldenburg, Hannover, Wiesbaden, and Lüneburg). Tumor type was adenocarcinoma in 112 (78 %) cases and squamous cell carcinoma in 31 (22 %). Tumor localization was as follows: proximal 3, mid esophagus 7, and distal third 133. Histological correlation either through EMR or surgery was available. In all patients, pretherapeutic uT and uN classifications were compared to pT/pN classification obtained from surgically (esophagectomy, n = 93) or endoscopically (EMR, n = 50) resected tissue. RESULTS: Overall, accuracy of uT classification was 60 % and of uN classification was 74 %. Sensitivity, specificity, and accuracy rates for local tumor extension were as follows (%): T1: 68/97/83; T2: 39/84/75; T3: 72/81/79; T4: 13/97/93; T1/2: 73/81/75; T3/4: 78/82/81. Relating to positive lymph node detection, sensitivity and specificity were 76 and 71 %, respectively. CONCLUSIONS: Miniprobe EUS is an established method for the staging of esophageal tumors. Our large multicenter cohort shows a solid accuracy of miniprobe EUS with respect to differentiating locally advanced from limited cancer and assisting to determine the treatment regimen in the era of neoadjuvant therapy; consequently, 78 % of patients would have been assigned to the adequate therapeutic regimen, whereas 11 % of patients would have been overtreated and 11 % undertreated.

Endoscopic transpapillary biopsies are of limited value in the diagnostics of bile duct strictures of unknown etiology-results of a histopathologically controlled study in 312 patients.

BACKGROUND/AIMS: Our investigation aimed to evaluate the impact of endoscopic transpapillary forceps biopsies (ETP) in bile duct strictures of unknown etiology based on the largest European patient cohort at a tertiary referral center. To date only studies with limited patient numbers exist. METHODOLOGY: Three-hundred-and-twelve patients (162 males, 150 females, mean age 62±12.7 years) with bile duct strictures of unknown etiology were examined with ETP. Sensitivity, specificity and accuracy of ETP were compared to the definite diagnosis proved by histopathology of surgical resection specimens or long-term follow-up of those patients not undergoing surgery. RESULTS: Using ETP a correct pe-interventional diagnosis was achieved in 211 out of 312 patients resulting in an accuracy rate of 67.6%. Eighty-six out of 187 malignant stenoses were correctly diagnosed by ETP, giving rise to sensitivity and specificity rates of 46 and 100%, respectively. Sensitivity of ETP in cholangiocellular carcinoma was significantly superior to that in pancreatic carcinoma (52.5% vs. 35.6%, p = 0.026). Sensitivity and accuracy rates of ETP did not depend on the localization of the stenosis in the common bile duct. CONCLUSIONS: ETP alone is not reliable enough in diagnosing bile duct malignancies as shown by low sensitivity and accuracy rates (false-negative rate of 32%).

Teaching ultrasound in a curricular course according to certified EFSUMB standards during undergraduate medical education: a prospective study.

BACKGROUND: As a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University. METHODS: 240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method. RESULTS: There was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students' self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students' DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies. CONCLUSIONS: Training ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.

Unmasking of Metamizole-induced Liver Injury by Simult aneous Development of Characteristic Agranulocytosis.

BACKGROUND: Metamizole is one of the most used analgesic, antipyretic, and spasmolytic agents in many countries worldwide. While metamizole-induced agranulocytosis is an, albeit seldom, well-known adverse event, metamizole-associated drug-induced liver injury has been reported rarely in the literature and hence often remains unconsidered. Here, we present a unique case where metamizole-induced hepatotoxicity got unmasked by the simultaneous development of characteristic agranulocytosis. CASE REPORT: A 22-year-old woman without known conditions presented with a new onset of fever, jaundice, and maculopapular rash and explicitly denied intake of any new substances. Laboratory tests showed liver injury, granulopenia, and positive anti-nuclear and anti-mitochondrial (AMA-M2) antibodies. Liver biopsy revealed a histological pattern characteristic of drug-induced liver injury and bone marrow biopsy, the classical picture of metamizole-induced agranulocytosis. Indeed the in-depth interview of the patient unveiled metamizole consumption over the last two months. Therefore, we could diagnose metamizole-induced hepato- and myelotoxicity. Accordingly, steroid therapy led to normalization of liver parameters and stimulation with granulocyte colony- stimulating factor to leukocyte recovery. CONCLUSION: This case report is intended to increase the awareness of metamizole-associated druginduced liver injury which should always be kept in mind due to its occasionally life-threatening course. Diagnosis can be difficult particularly if anamnesis and written records are without hints for prior metamizole intake.

Enhanced monitoring and detection of recent genotype 3 hepatitis E virus infection through urine antigen testing.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis. Numerous studies have investigated the dynamics of HEV infection markers, but the most suitable marker for diagnosing ongoing or recent HEV infection remains to be determined. Recent evidence suggests that serum antigen testing is superior to serum IgM and RNA quantification. Moreover, it has been found that infected individuals excrete HEV antigen in significant quantities through urine. To address this question, we conducted a longitudinal analysis involving 16 patients with acute or chronic HEV infection in an area where genotype 3 HEV is prevalent. Our findings indicate that the diagnostic and monitoring capabilities of antigen testing for HEV infection can be further enhanced by measuring it in urine. Additionally, we were able to demonstrate that this enhancement is likely due to the presence of HEV-reactive IgG in blood plasma, which hampers efficient detection of HEV antigen through sandwich ELISA. In conclusion, urine-based antigen testing appears to be superior to measuring anti-HEV antibodies or viral RNA for diagnosing suspected HEV infection and monitoring ongoing infections.